ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1049G>A (p.Arg350Gln) (rs190786280)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000535074 SCV000632818 uncertain significance Multiple fibrofolliculomas 2020-09-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 350 of the FLCN protein (p.Arg350Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs190786280, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with FLCN-related conditions. ClinVar contains an entry for this variant (Variation ID: 134432). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000573718 SCV000673412 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-13 criteria provided, single submitter clinical testing The p.R350Q variant (also known as c.1049G>A), located in coding exon 6 of the FLCN gene, results from a G to A substitution at nucleotide position 1049. The arginine at codon 350 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001562933 SCV001785779 uncertain significance not provided 2020-08-14 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24728327)
ITMI RCV000121113 SCV000085281 not provided not specified 2013-09-19 no assertion provided reference population

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